Fast Approximate Quantification of Endovascular Stent Graft Displacement Forces in the Bovine Aortic Arch Variant.

PURPOSE: Displacement forces (DFs) identify hostile landing zones for stent graft deployment in thoracic endovascular aortic repair (TEVAR). However, their use in TEVAR planning is hampered by the need for time-expensive computational fluid dynamics (CFD). We propose a novel fast-approximate computation of DFs merely exploiting aortic arch anatomy, as derived from the computed tomography (CT) and a measure of central aortic pressure. MATERIALS AND METHODS: We tested the fast-approximate approach against CFD gold-standard in 34 subjects with the "bovine" aortic arch variant. For each dataset, a 3-dimensional (3D) model of the aortic arch lumen was reconstructed from computed tomography angiography and CFD then employed to compute DFs within the aortic proximal landing zones. To quantify fast-approximate DFs, the wall shear stress contribution to the DF was neglected and blood pressure space-distribution was averaged on the entire aortic wall to reliably approximate the patient-specific central blood pressure. Also, DF values were normalized on the corresponding proximal landing zone area to obtain the equivalent surface traction (EST). RESULTS: Fast-approximate approach consistently reflected (r2=0.99, p<0.0001) the DF pattern obtained by CFD, with a -1.1% and 0.7° bias in DFs magnitude and orientation, respectively. The normalized EST progressively increased (p<0.0001) from zone 0 to zone 3 regardless of the type of arch, with proximal landing zone 3 showing significantly greater forces than zone 2 (p<0.0001). Upon DF normalization to the corresponding aortic surface, fast-approximate EST was decoupled in blood pressure and a dimensionless shape vector (S) reflecting aortic arch morphology. S showed a zone-specific pattern of orientation and proved a valid biomechanical blueprint of DF impact on the thoracic aortic wall. CONCLUSION: Requiring only a few seconds and quantifying clinically relevant biomechanical parameters of proximal landing zones for arch TEVAR, our method suits the real preoperative decision-making process. It paves the way toward analyzing large population of patients and hence to define threshold values for a future patient-specific preoperative TEVAR planning.

A Deep Learning-Based and Fully Automated Pipeline for Thoracic Aorta Geometric Analysis and Planning for Endovascular Repair from Computed Tomography.

Feasibility assessment and planning of thoracic endovascular aortic repair (TEVAR) require computed tomography (CT)-based analysis of geometric aortic features to identify adequate landing zones (LZs) for endograft deployment. However, no consensus exists on how to take the necessary measurements from CT image data. We trained and applied a fully automated pipeline embedding a convolutional neural network (CNN), which feeds on 3D CT images to automatically segment the thoracic aorta, detects proximal landing zones (PLZs), and quantifies geometric features that are relevant for TEVAR planning. For 465 CT scans, the thoracic aorta and pulmonary arteries were manually segmented; 395 randomly selected scans with the corresponding ground truth segmentations were used to train a CNN with a 3D U-Net architecture. The remaining 70 scans were used for testing. The trained CNN was embedded within computational geometry processing pipeline which provides aortic metrics of interest for TEVAR planning. The resulting metrics included aortic arch centerline radius of curvature, proximal landing zones (PLZs) maximum diameters, angulation, and tortuosity. These parameters were statistically analyzed to compare standard arches vs. arches with a common origin of the innominate and left carotid artery (CILCA). The trained CNN yielded a mean Dice score of 0.95 and was able to generalize to 9 pathological cases of thoracic aortic aneurysm, providing accurate segmentations. CILCA arches were characterized by significantly greater angulation (p = 0.015) and tortuosity (p = 0.048) in PLZ 3 vs. standard arches. For both arch configurations, comparisons among PLZs revealed statistically significant differences in maximum zone diameters (p < 0.0001), angulation (p < 0.0001), and tortuosity (p < 0.0001). Our tool allows clinicians to obtain objective and repeatable PLZs mapping, and a range of automatically derived complex aortic metrics.

Poor concordance between definitions of type III arch and implications for risk prediction and assessment for carotid artery stenting.

OBJECTIVE: The type III arch configuration has been inconsistently reported as a stroke risk factor during carotid artery stenting. However, at least three different methods for the definition of type III arch can be identified in the literature, related to the level of the origin of the innominate artery (IA). According to Casserly's definition, a type III arch presents with an origin of the IA below the horizontal plane of the inner curvature. According to Madhwal's definition, a type III arch has a distance greater than twice the diameter of the left common carotid artery between the highest point of the arch and the origin of the IA. According to MacDonald's definition, a type III arch presents with a distance of ≥2 cm between the highest point of the arch and the origin of the IA. Our aim was to assess the level of concordance between these different methods. METHODS: Anonymized thoracic computed tomography scans of 100 healthy patients were reviewed. Two of us independently stratified the selected cases as a type I to III arch, according to the three considered definitions. The interobserver level of concordance for each type III arch classification and level of concordance among the three definitions were assessed. RESULTS: The 100 selected patients (64% male) were 76 ± 7 years old. For each definition, the interobserver repeatability was almost perfect for all three (Madhwal, κ = 0.81; 95% confidence interval [CI], 0.71-0.99; MacDonald, κ = 0.82; 95% CI, 0.72-0.92; Casserly, κ = 0.84; 95% CI, 0.74-0.93). The level of concordance among the different definitions was very low (Madhwal vs MacDonald, 85% [P = .002]; 33% for type III arch; Madhwal vs Casserly, 60% [P < .0001]; 12% for type III arch; MacDonald vs Casserly, 75% [P < .0001]; 12% for type III arch). CONCLUSIONS: The three definitions of the type III arch have a very low level of concordance, which might account for the varying clinical relevance of this configuration. Our findings have relevant implications for risk prediction for carotid artery stenting based on the presence of a type III arch, for comparisons of the results from different studies, and for comparisons of different datasets from multicenter trials.

Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial.

BACKGROUND: Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. METHODS: A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. RESULTS: In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6-24.0, P = 0.52) and 22.4% (97.5% CI: 17.2-28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. CONCLUSIONS: Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).

Geometric Pattern of Proximal Landing Zones for Thoracic Endovascular Aortic Repair in the Bovine Arch Variant.

OBJECTIVE: The aim was to investigate whether the "bovine" aortic arch (i.e. arch variant with a common origin of the innominate and left carotid artery (CILCA)) is associated with a consistent geometric configuration of proximal landing zones for thoracic endovascular aortic repair (TEVAR). METHODS: Anonymised thoracic computed tomography (CT) scans of healthy aortas were reviewed to retrieve 100 cases of CILCA. Suitable cases were stratified according to type 1 and 2 CILCA, and also based on type of arch (I, II, and III). Further processing allowed calculation of angulation and tortuosity of the proximal landing zones. Centre lumen line lengths of each proximal landing zone were measured in a view perpendicular to the centre line. All geometric features were compared with those measured in healthy patients with a standard arch configuration (n = 60). Two senior authors independently evaluated the CT scans, and intra- and interobserver repeatability were assessed. RESULTS: The 100 selected patients (63% male) were 71.4 ± 7.7 years old. Type 1 CILCA (62/100) was more prevalent than type 2 CILCA (38/100), and the two groups were comparable in age (p = .11). Zone 3 presented a severe angulation (i.e. > 60°), which was greater than in Zone 2 (p < .001), and a consistently greater tortuosity than Zone 2 (p = .003). This pattern did not differ between type 1 and type 2 CILCA. A greater tortuosity was also observed in Zone 0, which was related to increased elongation of the ascending aorta (i.e. Zone 0), than the standard configuration. The CILCA had an overall greater elongation, and Zone 2 also was specifically longer. When stratifying by type of arch, reversely from Type III to Type I, the CILCA presented a gradual flattening of its transverse tract, which entailed a consistent progressive elongation (p = .03) and kinking of the ascending aorta, with a significant increase of Zone 0 angulation to even a severe degree (p = .001). Also, from Type III to Type I, Zone 2 presented a progressively shorter length (p = .004), which was associated with increased tortuosity (p < .05). Mean intra- and interobserver differences for angulation measurements were 1.4° ± 6.8° (p = .17) and 2.0° ± 10.1° (p = .19), respectively. CONCLUSION: CILCA presents a consistent and peculiar geometric pattern compared with standard arch configuration, which provides relevant information for TEVAR planning, and may have prognostic implications.

Computational Fluid Dynamics Modeling of Proximal Landing Zones for Thoracic Endovascular Aortic Repair in the Bovine Arch Variant.

BACKGROUND: To assess the endograft displacement forces (DF), which quantify the forces exerted by the pulsatile blood flow on the vessel wall and transmitted on the terminal fixation site of the endograft after its deployment in proximal landing zones (PLZs) of the bovine aortic arch variant. METHODS: Thirty healthy aortic computed tomographic angiographies of subjects with bovine arch configuration (10 per type of arch, I-III) were selected for the purpose of the study. A 3-dimensional model of the aortic arch lumen was reconstructed. Computational fluid dynamics modeling was then used to compute DF magnitude and orientation (i.e., x, y, and z axes) in PLZs of each case. DF values were normalized to the corresponding aortic wall area to estimate equivalent surface traction (EST). RESULTS: DF were highest in zone 0, consistently with the greater surface area. DF in zone 3 were much greater than in zone 2 because of a 3-fold greater upward component (z axis) (P < 0.001), being therefore mainly oriented orthogonally to the aortic blood flow and to the vessel longitudinal axis in that zone. EST progressively increased from zone 0 toward more distal PLZs, with EST in zone 3 being much greater than that in zone 2 (P < 0.001). The same pattern was observed after stratification by type of arch. CONCLUSIONS: The bovine arch is associated with a consistent fluid dynamic pattern, which identifies in zone 3 an unfavorable biomechanical environment for endograft deployment.

Type III Arch Configuration as a Risk Factor for Carotid Artery Stenting: A Systematic Review of Contemporary Guidelines on Management of Carotid Artery Stenosis.

BACKGROUND: Type III arch configuration is frequently reported as a stroke risk factor for carotid angioplasty and stenting (CAS). We reviewed contemporary guidelines on management of carotid artery stenosis to assess the clinical relevance attributed to this anatomic feature in current clinical practice. METHODS: The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The PubMed, EMBASE, and Web of Science databases were searched to identify all guidelines on extracranial carotid disease published between January 2008 and March 2020. A total of 435 articles were screened. For multiple guidelines from the same writing group, only the most recent updated version was considered. Eighteen documents were identified for qualitative analysis. RESULTS: Four guidelines specifically reported type III arch as a predictive factor of periprocedural complications after CAS. Two of them also provided a low level of evidence of their recommendation. None of the documents indicated the exact criteria for aortic arch classification. Three different methods to describe type III arch configuration were identified. CONCLUSIONS: Type III arch configuration is inconsistently included among stroke risk factors for CAS in contemporary guidelines, and variably defined. Further studies on the level of concordance between the 3 existing definition criteria are warranted.

Impact of the Bird-Beak Configuration on Postoperative Outcome After Thoracic Endovascular Aortic Repair: A Meta-analysis.

Purpose: To investigate the association between the bird-beak configuration (BBC), a wedge-shaped gap between the undersurface of a thoracic endograft and the lesser curvature of the arch after thoracic endovascular aortic repair (TEVAR), and postoperative outcome after TEVAR. Methods: The study was performed according to the PRISMA guidelines. The PubMed, EMBASE, and Cochrane databases were searched to identify all case series reporting BBC after TEVAR between 2006 and April 2018. Data analysis was performed considering the difference in the risk of complications for presence vs absence of BBC. After screening 1633 articles, 21 studies were identified that matched the selection criteria; 12 of these reported detailed information to investigate the postoperative outcome using proportion meta-analysis with a random effects model. The pooled risk difference is reported with the 95% confidence interval (CI). Heterogeneity of the included studies was assessed with the I2 statistic (low 25%, medium 50%, high 75%). Results: Complications occurred within a range of 0 to 72 months in 14.7% (95% CI 7.4% to 27.3%) of patients with BBC and in 6.3% (95% CI 2.5% to 15.4%) of patients without BBC. A cumulative incidence could not be assessed. The summary risk difference was 11.1% (95% CI -0.1% to 22.3%, p=0.052). There was significant heterogeneity (I2=85.6%). The Egger test did not show evidence of publication bias (p=0.975). When specifically considering type Ia endoleak and endograft migration, the risk difference between BBC and non-BBC patients was 8.2% (95% CI 0.3% to 16.1%, p=0.042; I2=69.0%). The specific risk difference for endograft collapse/infolding and thrombosis was 3.7% (95% CI -3.5% to 11.1%, p=0.308; I2=10.2%). Conclusion: At present the literature does not provide statistical evidence to establish an overall prognostic value of the BBC. Nevertheless, the BBC appears to be associated with a high risk of type Ia endoleak and endograft migration, which warrants specific and long-term surveillance. Clinically relevant values for BBC grading should be established to perhaps define indications for preemptive treatment based on the presence of BBC only.

Current evidence in predictors of aortic growth and events in acute type B aortic dissection.

OBJECTIVES: Acute type B aortic dissection can have a stable course or evolve into aneurysm and subsequent adverse events. The aim of this systematic review was to analyze the morphologic predictors of an adverse course to establish their validity based on consistency of results. METHODS: Fifty-one studies were included in this review, reporting on aortic size, false lumen (FL) size, primary entry tear (ET) size and location, status of FL thrombosis, number of ETs, branch vessels involvement, and FL longitudinal extent. RESULTS: Some predictors showed good consistency, whereas others did not. Aortic size was the most investigated predictor. A larger diameter at presentation predicted worse outcomes, with few exceptions. Both FL size and size relative to true lumen size also predicted an adverse course, although a standardized measurement method was not used. Regarding primary ET size and location, evidence was sparse and somewhat conflicting. Although FL complete thrombosis was consistently associated with a more benign course, the role of partial thrombosis remained unclear and the concept of FL saccular formation might account for the inconsistency, but further evidence is needed. A higher number of re-entry tears was considered to be protective against false channel expansion, but results need to be confirmed. The predictive role of branch vessels involvement and FL longitudinal extent remain controversial. CONCLUSIONS: Among several predictors of aortic growth and events in acute type B aortic dissection, controversial and even conflicting results have been described. Consistent evidence has been demonstrated only for two predictors: aortic size at presentation is associated with adverse events and total FL thrombosis has a protective role.

The Modified Arch Landing Areas Nomenclature (MALAN) Improves Prediction of Stent Graft Displacement Forces: Proof of Concept by Computational Fluid Dynamics Modelling.

OBJECTIVE: To assess whether the Modified Arch Landing Areas Nomenclature (MALAN), which merges Ishimaru's map with the Aortic Arch Classification, predicts the magnitude of displacement forces and their orientation in proximal landing zones for TEVAR. METHODS: Computational fluid dynamic (CFD) modelling was employed to prove the hypothesis. Healthy aorta CT angiography scans were selected based on aortic arch geometry to reflect Types I to III arches equally (each n = 5). CFDs were used to compute pulsatile displacement forces along the Ishimaru's landing zones in each aorta including their three dimensional orientation along the upward component and sideways component. Values were normalised to the corresponding aortic wall area to calculate equivalent surface traction (EST). RESULTS: In Types I and II arches, EST did not change across proximal landing zones (p = .297 and p = .054, respectively), whereas in Type III, EST increased towards more distal landing zones (p = .019). Comparison of EST between adjacent zones, however, showed that EST was greater in 3/II than in 2/II (p = .016), and in 3/III than in 2/III (p = .016). Notably, these differences were related to the upward component, that was four times greater in 3/II compared with 2/II (p < .001), and five times greater in 3/III compared with 2/III (p < .001). CONCLUSION: CFD modelling suggests that MALAN improves discrimination of expected displacement forces in proximal landing zones for TEVAR, which might influence clinical outcomes. The clinical relevance of the finding, however, remains to be validated in a dedicated post-operative outcome analysis of patients treated by TEVAR of the arch.

A geometric reappraisal of proximal landing zones for thoracic endovascular aortic repair according to aortic arch types.

OBJECTIVE: This study assessed whether the additional use of the aortic arch classification in type I, II, and III may complement Ishimaru's aortic arch map and provide valuable information on the geometry and suitability of proximal landing zones for thoracic endovascular aortic repair. METHODS: Anonymized thoracic computed tomography scans of healthy aortas were reviewed and stratified according to the aortic arch classification, and 20 of each type of arch were selected. Further processing allowed calculation of angulation and tortuosity of each proximal landing zone. Data were described indicating both proximal landing zone and type of arch (eg, 0/I). RESULTS: Angulation was severe (>60°) in 2/III and in 3/III. Comparisons among the types of arch showed an increase in proximal landing zones angulation (P < .001) and tortuosity (P = .009) depending on the type of arch. Comparisons within type of arch showed no change in angulation and tortuosity across proximal landing zones within type I arch (P = .349 and P = .409), and increases in angulation and tortuosity toward more distal proximal landing zones within type II (P = .003 and P = .043) and type III (P < .001 in both). CONCLUSIONS: The aortic arch classification is associated with a consistent geometric pattern of the aortic arch map, which identifies specific proximal landing zones with suboptimal angulation for stent graft deployment. Arches II and III also appear to have progressively less favorable anatomy for thoracic endovascular aortic repair compared with arch I.

Vitamin D Deficiency Is Associated with Increased Osteocalcin Levels in Acute Aortic Dissection: A Pilot Study on Elderly Patients.

An imbalance between degradation and reconstruction of the aortic wall is one of the leading causes of acute aortic dissection (AAD). Vitamin D seems an intriguing molecule to explore in the field of AAD since it improves endothelial function and protects smooth muscle cells from inflammation-induced remodeling, calcification, and loss of function, all events which are strongly related to the aging process. We quantified 25-hydroxy vitamin D, calcium, parathormone, bone alkaline phosphatase, and osteocalcin levels in 24 elderly AAD patients to identify a potential pathological implication of these molecules in AAD. Median 25-hydroxy vitamin D (10.75 ng/mL, 25th-75th percentiles: 6.86-19.23 ng/mL) and calcium levels (8.70 mg/dL, 25th-75th percentiles: 7.30-8.80 mg/dL) suggested hypovitaminosis D and a moderate hypocalcemia. Thirty-eight percent of AAD patients had severe (<10 ng/mL), 38% moderate (10-20 ng/mL), and 24% mild 25-hydroxy vitamin D deficiency (20-30 ng/mL). A significant inverse correlation was observed between 25OHD and osteocalcin levels. All the other molecules were unchanged. A condition of hypovitaminosis D associated to an increase in osteocalcin levels is present in AAD patients. The identification of these molecules as new factors involved in AAD may be helpful to identify individuals at high risk as well to study preventing strategies.

Temporary Transvenous Pacemaker Implantation during Carotid Endarterectomy in Patients with Trifascicular Block.

BACKGROUND: The risk of severe perioperative bradyarrhythmias in patients with chronic left bundle branch, or bifascicular block, and an additional first-degree atrioventricular block undergoing carotid endarterectomy (CEA) has never been specifically addressed. In this study, we aimed to investigate whether these conduction abnormalities entail an increased risk of hemodynamic compromise during CEA and the role of temporary transvenous pacemaker (TTVPM) implantation as a prophylactic measure in this subgroup of patients. METHODS: Between June 2006 and June 2013, 37 CEAs were performed in 31 patients (29 men, mean age 76 ± 6 years), in whom a TTVPM was implanted for a trifascicular block. Thirty-seven concurrent, consecutive patients operated for other vascular pathologies also with a prophylactic TTVPM for an asymptomatic trifascicular block served as controls. Adverse events were considered: pacemaker activation, block progression, bradycardia ≤40 beats/min, and asystole. RESULTS: Study and control groups were overall comparable. No perioperative mortality was recorded. All patients undergoing CEA were asymptomatic for syncope preoperatively. Among them, in 34 cases, indication for TTVPM was based on preoperative EKG, and in 4, a pacemaker activation was recorded. Three additional patients were also included in the study group in whom TTVPM was implanted due to the occurrence of adverse advents, and not prophylactically. In 2 of these, severe bradycardia with eventual asystole occurred intraoperatively. In both cases, the procedure was discontinued and rescheduled for the following day after a TTVPM was implanted. In the last additional case, the patient had a block progression on day 1 after an uneventful CEA and was emergently treated with a TTVPM. Overall, 7 adverse events were recorded in the study group, and none in the control group (P < 0.011). Morbidity in the CEA group also included 1 myocardial infarction, 1 minor stroke, 1 surgical revision for cervical hematoma, 1 new-onset atrial fibrillation, and 1 femoral artery pseudoaneurysm. CONCLUSIONS: In our experience, TTVPM implantation was a clinically useful adjunct in patients with trifascicular block submitted to CEA, as compared with other vascular surgical procedures. However, the risks inherent to CEA in this subgroup of patients suggest that surgical treatment may not be warranted for those with asymptomatic carotid disease.

Activities at Thoracic Aortic Research Center, IRCCS Policlinico San Donato.

The Thoracic Aortic Research Center (TARC) of the IRCCS Policlinico San Donato (PSD) aims to promote research on thoracic aortic diseases, to disclose the scientific knowledge and clinical experience and to develop new scientific paths within the Hospital and the aortic community, in collaboration with other national and international centres. Thoracic Aortic Research Center collaborates with many centres in both Europe (e.g. University of Utrecht, the Netherlands) and the USA (e.g. University of Michigan). This has led to multiple highly regarded publications in respected cardiovascular journals and has led to several PhD programmes resulting in doctorate degrees. Within Italy, in association with the Bioengineering School of the University of Pavia, TARC has founded the "BETA-lab" (Biomechanics for Endovascular Treatment of the Aorta laboratory), where MDs, Bioengineers, and PhD fellows conduct experimental studies using in vitro/ex vivo models of the physiologic aorta and aortic diseases. Furthermore, a database (iCardiocloud) where the medical imaging of cardiovascular patients from the PSD is structured, for in silico analysis utilizing computational fluid dynamics, and in vitro studies using also 3D printed aortic models. With the role of principal investigator or co-investigator, TARC at PSD has been participating in other several projects, including the International Registry of Acute Aortic Dissection, the International Aortic Arch Surgery Study Group, the European Registry of Endovascular Aortic Repair Complications, the ADSORB and ASSIST trials, and the GREAT registry. International collaborations have included also studies on predictors of aortic growth after dissection with the Yale University and University of Virginia, and on aortic biomarkers with the University of Tokyo.

Peripheral baroreflex and chemoreflex function after eversion carotid endarterectomy.

OBJECTIVE: This study assessed the long-term effect of the eversion technique for carotid endarterectomy (e-CEA) on arterial baroreflex and peripheral chemoreflex function. METHODS: The study included 13 patients who underwent, between 2001 and 2006, bilateral e-CEA and 16 who underwent bilateral standard CEA (s-CEA) to eliminate the complicating effects of intact contralateral carotid sinus function. Exclusion criteria were age >70 years, diabetes mellitus, chronic pulmonary disease, ischemic cardiac disease or medical therapy with ß-blockers, cardiac arrhythmia, neurologic deficits, carotid restenosis, and previous neck or chest surgery or irradiation. Young and aged-matched healthy individuals were recruited as controls. All patients underwent standard cardiovascular reflex tests, including lying-to-standing, orthostatic hypotension, deep breathing, and Valsalva maneuver. Autonomic cardiovascular modulation was indirectly evaluated by spectral analysis of heart rate variability and systolic arterial pressure variability. The chemoreflex sensitivity to hypoxia was obtained during classic rebreathing tests from the slopes of the linear regression of minute ventilation (VE) vs arterial oxygen saturation measured by pulse oximetry (SpO2%) and partial pressure of end-tidal oxygen (PetO2). RESULTS: Patients (16 men; age, 62.4 ± 8.0 years) were enrolled after a mean interval of 24 ± 17 months from the last CEA. All were asymptomatic, and results of standard tests were negative. Residual baroreflex performance was documented in both patient groups, although reduced, compared with young controls. Notably, baroreflex sensitivity (msec/mm Hg) was better maintained after e-CEA than after s-CEA at rest (young controls, 19.93 ± 9.50; age-matched controls, 7.75 ± 5.68; e-CEA, 13.85 ± 14.54; and s-CEA, 3.83 ± 1.15; analysis of variance [ANOVA], P = .001); and at standing (young controls, 7.83 ± 2.55; age-matched controls, 3.71 ± 1.59; e-CEA, 7.04 ± 5.62; and s-CEA 3.57 ± 3.80; ANOVA, P = .001). Similarly, chemoreflex sensitivity to hypoxia was maintained in both patient groups, which did not differ from each other, and was reduced compared with controls (controls vs patient groups ΔVE/ΔSpO2: -1.37 ± 0.33 vs -0.33 ± 0.08 and SpO2% -0.29 ± 0.13 L/min; P = .002; ΔVE/ΔPetO2: -0.20 ± 0.1 vs -0.01 ± 0.0 and -0.07 ± 0.02 L/min/mm Hg; P = .04, ANOVA with least significant difference correction for multiple comparisons). CONCLUSIONS: Our data show that e-CEA, even when performed on both sides, preserves baroreflexes and chemoreflexes and, therefore, does not confer permanent carotid sinus denervation. Also, e-CEA does not increase long-term arterial pressure variability, and this suggests that perioperative hemodynamic derangements can be attributed to the temporary effects of surgical trauma.